Dr. McChargue's short-term goals are to enhance the theoretical, methodological, and statistical skills that he needs to study the determinants of nicotine self-administration in smokers with comorbid psycohpathology. His long-term goals are to develop an independent laboratory, as well as a network of research collaborators devoted to advancing our understanding of nicotine dependence and training fixture clinical researchers. The proposed studies will evaluate two premises about smokers with a history of depression that have been assumed but not directly tested. The first proposition is that depression-prone smokers experience greater than normal cigarette cravings when exposed to negative affect cues. The second proposition is that the dysphoria-reducing effects of self-administering nicotine are more potent for depression-prone than non-prone smokers. Study 1 aims to compare the reactivity of smokers with and without history of depression to cues involving smoking paraphernalia and negative mood. Reactivity will be measured via self-report, behavioral and physiological indices of craving. The hypothesis is that depression-prone smokers will show heightened cue reactivity in general, but will be especially reactive to dysphoric mood cues. The aim of Study 2 is to compare the degree to which smoking a nicotinized versus a denicotinized cigarette alleviates experimentally induced dysphoria in smokers with versus without a history of depression. The hypothesis is that nicotine's potency as a negative reinforcer (i.e., its ability dispel dysphoric mood) will be enhanced for smokers who have a history of depression, as compared to those who lack such a history. These studies will be the first to systematically examine craving responses in depression-prone smokers and to quantify the dysphoria-reducing effects of nicotine administration for this population. Results should increase understanding of mechanisms that mediate the high prevalence and persistence of smoking among depression-prone individuals, and may contribute to the development of novel treatments for this recalcitrant group of smokers.